The fundamental objective of this program is to characterize interactions between humans and poultry with a focus on zoonotic transmission of avian influenza viruses. Emphasis will be placed on small flock, semi-commercial poultry operations in two disparate ecosystems: the western United States, where avian influenza is rare, and central Indonesia, where H5N1 influenza virus infections of both humans and poultry have recently occurred. Our goal is to provide a better understanding of the factors which may promote human infection with avian influenza viruses and to enhance our ability to detect and mitigate such transmission. Specific aims for this work are to: (1) Characterize the distribution of and patterns of bird transport among semi-commercial flocks of chickens and ducks in Colorado and surrounding western states extending to the Mexican border, and assess how frequently and intimately humans interact with these birds. In the process of assembling such a dynamic mapping, we will obtain baseline data on the prevalence of influenza virus infection in the birds and an estimate of previous infections by avian influenza viruses in humans that interact with them. (2) Establish a system for active surveillance of influenza virus infection in humans and their associated poultry in central Indonesia, and delineate the role of human-poultry interactions in ransmission of influenza viruses. We will obtain estimates of infection rate and seroprevalence from both humans and poultry, and estimate the frequency of clinical and subclinical infection of both humans and birds. Genetic risk factors will be evaluated in a subset of humans in this locale. (3) Evaluate experimentally the influence of suboptimal avian vaccination on viral evolution by characterization of genotype and phenotype of H5N1 influenza viruses isolated from immunized birds undergoing subclinical infection. The work proposed in the US will provide a comprehensive understanding of human-poultry interactions and poultry movement in the large population of semi-commercial birds that are likely to be key in any control efforts following introduction of highly-pathogenic avian influenza into this country. The studies to be conducted in Indonesia will deliver estimates of the frequency of subclinical infections with avian influenza viruses, and will provide enhanced understanding of the epizootiology of such infections that can be applied to detection, prevention and control of such infections in this country. [unreadable] [unreadable] [unreadable] [unreadable]